title: Lymphodepletional strategies in transplantation.
abstract: Because lymphocytes were shown to mediate transplant rejection, their depletion has been studied as a mechanism of preventing rejection and perhaps inducing immunologic tolerance. Agents that profoundly deplete lymphocytes have included monoclonal antibodies, cytotoxic drugs, and radiation. We have studied several such agents but focused on antibodies that deplete not only peripheral blood lymphocytes, but also lymph node lymphocytes. Depletion of lymph node T lymphocytes appears to permit peripheral tolerance at least for T cells in animal models. Nevertheless, B-cell responses may be resistant to such approaches, and T memory cells are likewise relatively resistant to depleting antibodies. We review the experimental and clinical approaches to depletion strategies and outline some of the pitfalls of depletion, such as limitations of currently available agents, duration of tolerance, infection, and malignancy. It is notable that most tolerogenic strategies that have been attempted experimentally and clinically include depleting agents even when they are not named as the underlying strategy. Thus, there is an implicitly acknowledged role for reducing the precursor frequency of donor antigen-specific lymphocytes when approaching the daunting goal of transplant tolerance.
authors.affiliation: Department of Surgery, Division of Transplantation, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Page
authors.forename: Jean
authors.initials: J
authors.lastname: Kwun
authors.forename: Byoungchol
authors.initials: B
authors.lastname: Oh
authors.forename: Stuart
authors.initials: S
authors.lastname: Knechtle
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects*; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008212:Lymphocyte Depletion / Q000009:adverse effects / Q000379:methods*; D008232:Lymphoproliferative Disorders / Q000276:immunology; D009369:Neoplasms / Q000276:immunology; D009894:Opportunistic Infections / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects*; D014181:Transplantation Immunology
chemical_list: D007166:Immunosuppressive Agents